Non-selective Beta-adrenoceptor Blockade Research Articles

Food choice in hyperthyroidism: potential influence of the autonomic nervous system and brain serotonin precursor availability.

We explored energy and macronutrient intake in patients with Graves' hyperthyroidism. We specifically hypothesized that hyperthyroidism is associated with increased appetite for carbohydrates, because of enhanced sympathetic tone and diminished serotonin mediated neurotransmission in the brain. To test this hypothesis, we measured food intake by dietary history and food selected for lunch in the laboratory in 14 patients with Graves' hyperthyroidism. Twenty-four-hour catecholamine excretion was used as a measure of activity of the sympathetic nervous system (SNS) and the plasma [Trp]/[NAA] ratio was measured to estimate (rate limiting) precursor availability for brain 5-hydroxytryptamine synthesis. All measurements were repeated after the subjects had been treated to establish euthyroidism. In addition, the effects of nonselective beta-adrenoceptor blockade upon these parameters were studied to evaluate the influence of beta-adrenergic hyperactivity on food intake. Hyperthyroidism was marked by increased SNS activity and reduced plasma [Trp]/[NAA] ratio. Accordingly, energy intake was considerably and significantly increased in hyper vs. euthyroidism, which was fully attributable to enhanced carbohydrate consumption, as protein and fat intake were not affected. These results suggest that hyperthyroidism alters the neurophysiology of food intake regulation. Increased SNS activity and reduced Trp precursor availability for 5-hydroxytryptamine synthesis in the brain may drive the marked hyperphagia and craving for carbohydrates that appears to characterize hyperthyroid patients. Because propranolol did not affect food intake in hyperthyroidism, the potential effect of catecholamines on food intake might be mediated by alpha-adrenoceptors.

Cardiovascular effects of the novel Ca2+-sensitiser EMD 57033 in pigs at rest and during treadmill exercise.

1. To date no study has described the cardiovascular effects of increased myofilament Ca2+ responsiveness in awake animals both under resting conditions and during treadmill exercise. In the present study we therefore investigated the systemic, pulmonary and coronary haemodynamic actions of the Ca2+ sensitizer EMD 57033 in 16 chronically instrumented awake pigs at rest and during treadmill exercise, and compared these to the haemodynamic actions of the Ca2+ sensitizer/phosphodiesterase inhibitor pimobendan. 2. Under resting conditions EMD 57033 (0.2, 0.4 and 0.8 mg kg(-1) min(-1), i.v.) produced dose-dependent increases in LVdP/dt(max) (up to 65+/-17% (mean+/-s.e.mean), P < or = 0.05) and stroke volume (up to 20+/-3%, P < or = 0.05), with an increase in heart rate only after the highest dose (22+/-5%, P < or = 0.05), while mean aortic blood pressure and LVdP/dt(min) were not altered. EMD 57033 had also no effect on pulmonary vascular resistance, but produced dose-dependent decreases in systemic vascular resistance (32+/-4%, P < or = 0.05), and coronary vascular resistance (44+/-2%, P < or = 0.05). These effects were essentially unchanged when animals were pretreated with non-selective beta-adrenoceptor blockade, indicating that phosphodiesterase inhibition did not contribute to the positive inotropic actions of EMD 57033. 3. During exercise at 2, 3, and 4 km h(-1), the positive inotropic actions of EMD 57033 gradually waned at higher levels of exercise. This may have been caused by the exercise-induced increase in beta-adrenergic activity, because after pretreatment with propranolol the positive inotropic actions of EMD 57033 were preserved at all levels of exercise. In contrast, the positive inotropic and chronotropic effects of pimobendan were amplified during exercise, but were abolished (at rest) or markedly attenuated (during exercise) after pretreatment with propranolol. 4. The responses to EMD 57033 during exercise after combined alpha- and beta-adrenergic receptor blockade were not different from those after beta-adrenergic receptor blockade alone, indicating that the positive inotropic actions of EMD 57033 were not mediated via or did not depend on intact alpha-adrenergic receptor activity. 5. In conclusion, EMD 57033 increases left ventricular myocardial contractility in awake pigs. During exercise this effect is partially offset by the increased beta-adrenergic activity, with no effect of alpha-adrenergic activity, suggesting that EMD 57033 may be most effective in patients with severe loss of beta-adrenergic responsiveness.

Autonomic mechanisms underlying intraocular pressure changes during insulin-induced hypoglycaemia in normal human subjects: effects of pharmacological blockade

1. A fall in intraocular pressure is induced by acute hypoglycaemia in humans. The role of the autonomic nervous system in mediating this response was investigated in 24 normal volunteers in whom hypoglycaemia was induced with intravenous soluble insulin, under four experimental conditions: (1) control (n = 6), (2) non-selective alpha-adrenoceptor blockade (phentolamine) (n = 6), (3) non-selective beta-adrenoceptor blockade (propranolol) (n = 6) and (4) cholinergic blockade (atropine) (n = 6). Intraocular pressure was measured by using an applanation tonometer. In 12 subjects intraocular pressure was measured during each type of pharmacological blockade of similar duration without induction of hypoglycaemia, to assess the effects of individual antagonists. 2. In the control study intraocular pressure fell during hypoglycaemia from 15 +/- 1.0 to 10 +/- 1.3 mmHg (P less than 0.01) 10 min after the autonomic reaction. beta-Adrenoceptor blockade caused a reduction in intraocular pressure from 15 +/- 1.1 to 9 +/- 1.0 mmHg (P less than 0.001) before the administration of insulin, and when hypoglycaemia was induced intraocular pressure decreased further to 7 +/- 1.0 mmHg (P less than 0.05, compared with immediately before insulin). A decrease in intraocular pressure of similar magnitude was observed with propranolol alone (16 +/- 1.0 to 10 +/- 1.0 mmHg, P less than 0.05). 3. Cholinergic blockade had no immediate effect on intraocular pressure, and the reduction in intraocular pressure during hypoglycaemia was of similar magnitude to that observed during the control study.(ABSTRACT TRUNCATED AT 250 WORDS)

The role of α‐ and β‐adrenoceptor subtypes in mediating the effects of catecholamines on fasting glucose and insulin concentrations in the rat

1. The role of alpha- and beta-adrenoceptor subtypes in the regulation of plasma glucose and immunoreactive insulin (IRI) levels has been investigated in normal conscious fasted rats by employing selective agonists and antagonists. 2. Adrenaline (0.2 mg kg-1)-induced hyperglycaemia was abolished by the selective alpha 2-adrenoceptor antagonist idazoxan (1.0 mg kg-1), unaltered by non-selective beta-adrenoceptor blockade (propranolol, 1.0 mg kg-1) and potentiated by the selective alpha 1-adrenoceptor antagonist prazosin (0.3 mg kg-1). Adrenaline increased plasma IRI levels in the presence of idazoxan but not in the presence of either prazosin or propranolol. 3. The selective alpha 2-adrenoceptor agonists UK 14304 (0.1 and 0.3 mg kg-1) and BHT-920 (0.2 and 0.5 mg kg-1) elicited dose-dependent hyperglycaemic responses, but did not alter plasma IRI levels. UK 14304 (0.1 mg kg-1)-evoked hyperglycaemia was blocked by idazoxan but not by prazosin. 4. The selective alpha 1-adrenoceptor agonists methoxamine (0.3 mg kg-1) and phenylephrine (0.3 mg kg-1) failed to modify either plasma glucose or IRI levels. 5. Isoprenaline (0.2 mg kg-1) elicited hyperglycaemic and insulinotropic responses which were attenuated by propranolol (1.0 mg kg-1) and the selective beta 2-adrenoceptor antagonist ICI 118551 (1.0 mg kg-1), but not by the beta 1-selective antagonists atenolol (1.0 mg kg-1) and betaxolol (1.0 mg kg-1). 6. None of the antagonists per se affected basal plasma glucose or IRI concentrations, except prazosin (1.0 mg kg-1). 7. The results indicate that adrenoceptors do not appear to be involved in regulating basal plasma glucose and IRI concentrations in the fasted rat. However, the effects of catecholamines on these parameters are mediated by alpha 2- and beta 2-adrenoceptors, whereas alpha,- or beta l-adrenoceptors do not appear to be involved.

Metabolic, Electrocardiographic, and Hemodynamic Responses to Increased Circulating Adrenaline: Effects of Selective and Nonselective Beta Adrenoceptor Blockade

Twelve healthy male volunteers were given adrenaline infusions, 0.05 microgram/kg body weight/minute over one hundred twenty minutes (min), in order to achieve serum adrenaline concentrations comparable with those seen in acute myocardial infarction. The infusions were given on three occasions, at intervals of at least four weeks. Before the infusions the subjects were given, in random order, two days' pretreatment with placebo, a beta-1-selective adrenoceptor blocker (atenolol), or a nonselective beta blocker (propranolol) with each subject receiving each pretreatment. Six of the volunteers also had a fourth adrenaline infusion, after two days' pretreatment with a beta-2-selective beta blocker, ICI 118551. Adrenaline increased heart rate by 11 beats/min, increased systolic blood pressure by 10 mmHg, and decreased diastolic blood pressure by 15 mmHg. These changes were partly prevented by atenolol. Propranolol and ICI 118551 partly prevented the rise in systolic blood pressure but differed from atenolol in their effects on heart rate and diastolic blood pressure, causing falls in heart rate by 7 beats/min and 12 beats/min respectively, secondary perhaps to increases in diastolic blood pressure by 13 mmHg and 17 mmHg respectively. Adrenaline caused a prolongation of QTc duration by 0.03 second and a flattening of the T-wave amplitude by 1.04 mm. These changes in cardiac repolarization were partly inhibited by atenolol, but the effects of propranolol and ICI 118551 were greater, each causing a reduction of QTc and an increase in T-wave amplitude. During adrenaline infusion S-potassium declined by 0.60 mmol/L, S-magnesium by 0.05, S-calcium by 0.10, and S-phosphate by 0.24, but S-free fatty acids increased nearly threefold. All these changes were statistically significant and were presumably mediated mainly by the beta-2-adrenoceptor, for they were blocked more effectively by the beta-2-adrenoceptor blockers than by the selective beta-1-adrenoceptor blocker. B-glucose increased by 4.1 mmol/L, the increase being practically unaffected by the different pretreatments. These adrenaline-induced hemodynamic, electrocardiographic, and metabolic changes may predispose to arrhythmias and impair cardiac performance after a myocardial infarction. Nonselective beta blockers may be more effective in blocking the electrocardiographic and metabolic effects, but beta-1-selective beta blockers may have hemodynamic advantages.

Differential effects of non-specific beta-blockade and calcium antagonism on blood-clotting mechanisms

The effects of non-selective beta-blockade (timolol, 5 mg twice daily) and calcium antagonism (isradipine, 2.5 mg twice daily) on heart rate, blood pressure, platelet aggregation, fibrinolytic activity, and platelet cyclic adenosine monophosphate content were investigated in 10 patients with mild hypertension in a randomized, placebo-controlled, double-blind study. Each patient served as his or her own control, taking each drug in turn for two weeks. Both drugs lowered blood pressure to the same degree. During timolol treatment, however, platelet aggregation increased whereas isradipine resulted in a shortening of the euglobulin clot lysis time (p <0.05), indicating increased fibrinolytic activity. Platelet aggregation and fibrinolytic activity are modified by cyclic adenosine monophosphate. Since beta-adrenoceptors are present on platelets and endothelial cells, the differences in platelet behavior and fibrinolytic activity may reflect a decreased cyclic adenosine monophosphate production caused by non-selective beta-adrenoceptor blockade.

10 Adrenaline-induced amplification of sympathetic activity during rest and stress; inhibition by beta,-selective and non-selective beta-adrenoceptor blockade

10 Adrenaline-induced amplification of sympathetic activity during rest and stress; inhibition by beta,-selective and non-selective beta-adrenoceptor blockade

Prejunctional beta 2-adrenoreceptor blockade reduces nerve stimulation evoked release of endogenous noradrenaline in skeletal muscle in situ.

Prejunctional beta-adrenoceptor-mediated modulation of endogenous noradrenaline (NA) overflow elicited by sympathetic nerve stimulation was studied in blood-perfused canine gracilis muscle in situ. An attempt was made to subclassify these beta-adrenoceptors by comparing the effects of beta 1-selective (metoprolol) and non-selective (propranolol) beta-adrenoceptor blockade. Animals were pre-treated with desipramine and phenoxybenzamine in order to counteract possible influences of neuronal uptake and stimulation-evoked changes in vascular resistance on the diffusion of NA into the blood stream. Metoprolol did not decrease stimulation-evoked NA overflow, as compared with control experiments (-10 and -8%, respectively). However, propranolol reduced stimulation-evoked NA overflow by 30% in metoprolol pre-treated animals (P less than 0.05 vs. control experiments). Both antagonists elevated basal perfusion pressure, suggesting that vascular post-junctional beta 1- as well as beta 2-adrenoceptors are present. Propranolol increased stimulation-evoked vasoconstriction in metoprolol pre-treated animals, indicating that neuronally released NA may activate postjunctional beta 2-adrenoceptors under these experimental conditions. In conclusion, our findings suggest that NA release can be enhanced by activation of prejunctional beta 2-adrenoceptors in vivo.

Acute and Long-Term Hemodynamic Effects of Carvedilol, a Combined β-Adrenoceptor Blocking and Precapillary Vasodilating Agent, in Hypertensive Patients

The purpose of these studies was to investigate the hemodynamic effects of carvedilol, a compound with combined properties of nonselective beta-adrenoceptor blockade and precapillary vasodilatation. The acute effects were studied with invasive technique (dye dilution) in 10 patients taking 25 mg orally and noninvasively (forearm plethysmography) in 10 patients taking 25 mg and in 10 patients taking 50 mg orally, all with essential hypertension. Significant reductions of systolic and diastolic blood pressure (p less than 0.05-0.001) were observed in all groups. Total peripheral resistance (TPR) did not change acutely whereas resistance in the forearm was reduced by 16% (p less than 0.05; invasive group). When a comparison with propranolol (80 mg x 2) was made in a randomized double-blind placebo controlled trial in 30 patients, carvedilol acutely reduced blood pressure significantly by 13/6 mg Hg (25 mg) and 17/10 mm Hg (50 mg) in contrast to propranolol. Resistance in the forearm fell significantly with 50 mg carvedilol, whereas propranolol caused a significant rise. After 4 weeks, both compounds had reduced blood pressure significantly. Blood flow was still reduced with propranolol in contrast to the findings with carvedilol. In conclusion, the summary of these studies shows that carvedilol given orally has a useful antihypertensive effect both acutely and during prolonged treatment, and it has an attractive hemodynamic profile, in agreement with the hemodynamic findings in essential hypertension.

Reflex adrenergic inhibition of colonic motility in anesthetized rat caused by nociceptive stimuli of peritoneum. An alpha 2-adrenoceptor-mediated response.

Nociceptive stimulation of the peritoneum inhibits colonic motility via a sympathoadrenergic reflex. This sympathetic reflex most probably induces the inhibition indirectly via a presynaptic blockade of cholinergic transmission. To further clarify this reflex, colonic motility was continuously recorded by a volume method in rats exposed to nociceptive abdominal stimulation and intravenous drug administration. Intraabdominally applied HCl inhibited colonic motility, which was unaffected by nonselective beta-adrenoceptor blockade (propranolol). However, the nonselective alpha-adrenoceptor antagonist phentolamine and the selective alpha 2-adrenoceptor antagonist yohimbine restored motility. Spontaneous colonic motility was unaffected by the nonselective beta-adrenoceptor agonist (isoproterenol) and the selective alpha 1-adrenoceptor agonist (L-phenylephrine). On the other hand, a nonselective alpha-agonist (noradrenaline) and a selective alpha 2-adrenoceptor agonist (clonidine) inhibited spontaneous colonic motility. It is suggested that in the rat sympathetic reflex inhibition of colonic motility caused by abdominal nociception is mediated via presynaptic alpha 2-adrenoceptors inhibiting the excitatory cholinergic neurons.

Effect of selective and nonselective beta-adrenoceptor blockade on thermoregulation during prolonged exercise in heat

The effect of selective and nonselective β-adrenoceptor blockade on the thermoregulatory responses of 11 physically active, healthy, young adult men was studied during 2-hour block-stepping In heat. The trial consisted of 3 periods of 6 days each during which propranoloi (160 mg/day), atenoloi (100 mg) or matching placebo was administered in a randomized, double-blind crossover fashion. Propranolol and atenoloi induced similar, significant (p <0.001) increases in subjective ratings of perceived exertion. The mechanism of this Increased fatigue was not evident from the documented alterations in serum electrolyte, blood glucose and blood lactate levels or ventilatory parameters. Propranolol did, however, induce a postexercise delayed serum potassium reversion. Although rectal and mean skin temperature responses were essentially unaltered by β-adrenoceptor blockade during block-stepping, an increased total sweat loss was observed with propranolol (p <0.01 versus placebo) and to a lesser degree with atenoloi (p = not significant versus placebo). This indicates that persons receiving β-adrenoceptor blockers have an Increased need to adhere to a strict fluid-replacement regimen during exercise. This potentially adverse response was minimal with atenoloi In contrast to pronolol, and this in turn suggests the use of β 1-selective adrenoceptor blockers during prolonged exercise when adequate fluid replacement is not possible.

Effect of adrenaline on myocardial oxygen consumption during selective and non-selective beta-adrenoceptor blockade comparison of atenolol and pindolol

Effect of adrenaline on myocardial oxygen consumption during selective and non-selective beta-adrenoceptor blockade comparison of atenolol and pindolol

Haemodynamic effects of loud noise in hypertensive patients treated with combined beta-adrenoceptor blockade and precapillary vasodilatation.

The effects of acute exposure to noise on central and regional (calf and forearm) haemodynamics were studied during placebo therapy and during combined nonselective beta-adrenoceptor blockade and precapillary vasodilatation in 9 patients with essential hypertension. On placebo therapy a loud noise (105 dBA for 10 min) caused a significant increase in diastolic and mean arterial pressure due to vasoconstriction. There was also a significant increase of vascular resistance in the calf. After combined precapillary vasodilatation and non-selective beta-adrenoceptor blockade, the increase in blood pressure during stimulation with noise was not prevented. Thus, systolic as well as diastolic and mean arterial pressures increased significantly. This indicates a temporary resetting of the baroreceptors, allowing a higher level of blood pressure during stimulation with noise. Such a resetting would involve the central nervous system pathways of the baroreflex and this would explain why the peripherally active therapeutic principle--precapillary vasodilatation and beta-adrenoceptor blockade--was unable to inhibit the blood pressure response induced by noise.

Effects of beta 1-selective and nonselective beta-adrenoceptor blockade during exercise conditioning in healthy adults

The interaction of β 1-selective (cardioselective) and nonselective β 1-adrenoceptor blockade with exercise conditioning was investigated in 30 healthy adult persons. A double-blind protocol was used and the effects of atenolol (100 mg/day), propranolol (80 mg twice daily), and placebo were studied by treadmill testing (Bruce protocol) before and after a 2-month supervised program of dynamic exercise. Exercise tolerance was assessed by time and work performed to exhaustion. Subjects who received propranolol, but not those who received atenolol or placebo, showed an acutely impaired exercise tolerance after drug administration but before training (− 8 ± 4%, p < 0.05). All 3 groups showed significantly improved exercise capacity following training after drug treatment had been discontinued (atenolol, 22 ± 6% improvement; propranolol, 13 ± 6%; placebo, 10 ± 3%). However, when tested while still receiving medication, subjects who received propranolol failed to show significant improvement in exercise capacity. In contrast, patients who received atenolol and placebo improved significantly. The data indicate that enhancement of maximal work capacity by exercise conditioning can occur despite administration of either β 1-selective or nonselective β-adrenoceptor antagonists. However, the fatiguing effects of propranolol that were evident when work performance during propranolol therapy was compared with work performance while not receiving propranolol before the training program persists after training and may limit the net improvement in work capacity induced by exercise conditioning compared with the pretraining state.

Hemodynamic and metabolic responses to exercise after alpha 1-, beta 1-, and nonselective beta-adrenoceptor blockade in man

The effects of acute alpha 1-adrenoceptor blockade with prazosin, beta 1-adrenoceptor blockade with atenolol, and nonselective beta-adrenoceptor blockade with propranolol were compared in a placebo-controlled crossover study. The study involved measurement of the hemodynamic and metabolic responses to exercise after heavy exercise in order to induce skeletal muscle glycogen depletion and thus enhance the dependence on hepatic glucose output and circulating free fatty acids. Catecholamine responses to exercise were enhanced by glycogen depletion and by both beta-blocking drugs. Catecholamine levels were highest with propranolol; as a consequence, at high work loads, propranolol failed to produce a significant reduction in systolic blood pressure and elevated diastolic blood pressure. At high work loads, atenolol reduced systolic blood pressure but did not change diastolic blood pressure. Both beta blockers reduced free fatty acid levels, but only propranolol accelerated the fall of plasma glucose levels during “glycogen-depleted” exercise. In contrast, during exercise prazosin reduced systolic and diastolic blood pressures, and elevated heart rate and plasma catecholamines, particularly noradrenaline. Concomitantly, prazosin raised free fatty acid and lactate levels, and increased the plasma glucose level at a time when placebo therapy resulted in a steady fall in glucose levels. The results indicate important differences in the hemodynamic effects of cardioselective versus nonselective beta-blockade during long-term (or glycogen-depleted) exercise. The importance of beta 2-mediated hepatic glycogenolysis in man is confirmed. Acute alpha 1-blockade with prazosin induces reflex elevation of Catecholamine levels. There is no indication of an important role for an alpha 1-mediated mechanism in hepatic glucose production in man.

8 Responses of Glomerular Filtration, Renal Blood Flow and Salt-water Handling to Acute Cardioselective Versus Non-selective Beta-adrenoceptor Blockade

8 Responses of Glomerular Filtration, Renal Blood Flow and Salt-water Handling to Acute Cardioselective Versus Non-selective Beta-adrenoceptor Blockade

Effect of adrenaline on myocardial oxygen consumption during selective and non-selective beta-adrenoceptor blockade comparison of atenolol and pindolol

The effect of adrenaline on myocardial oxygen consumption (MVO2) during selective and non-selective beta-adrenoceptor blockade was examined in 26 patients with angina pectoris. Cardiac venous flow was measured by thermodilution and blood was sampled for metabolic studies. Thirteen patients were given atenolol 62.5 micrograms/kg i.v. and the other 13 patients pindolol 7.5 micrograms/kg i.v. Measurements were repeated before and during infusion of adrenaline 0.1 microgram/kg/min. Compared to the control situation, adrenaline increased MVO2 more in atenolol-treated (39%) than in pindolol-treated patients (11%). This was partly due to augmented external cardiac work. Arterial FFA was considerably increased in the atenolol group (105%), but was unchanged in the pindolol group, suggesting an additional metabolic mechanism. Thus, adrenaline stimulation, which is comparable to that found in acute myocardial infarction, increases MVO2 more during selective than non-selective beta-blockade.

The effect of selective and non-selective beta-adrenoceptor blockade, and of naloxone infusion, on the hormonal mechanisms of recovery from insulin-induced hypoglycaemia in man.

The rise in plasma adenosine-3',5'-monophosphate occurring in response to insulin induced hypoglycaemia in normal human subjects, was abolished by non-selective beta-adrenoceptor blockade but unaffected by selective beta 1-adrenoceptor blockade. This implies that the rise is secondary to beta 2-adrenoceptor stimulation. The abolition of this rise by non-selective beta-adrenoceptor blockade had no pronounced effect on the recovery from hypoglycaemia. Endogenous opiate receptor blockade with naloxone had no significant effect on the recovery from insulin induced hypoglycaemia, or the hormonal mechanisms involved.

Haemodynamic effects of cigarette smoking during chronic selective and non‐selective beta‐adrenoceptor blockade in patients with hypertension.

1 Haemodynamic effects of cigarette smoking before and during chronic treatment with propranolol and metoprolol were studied in 16 patients with essential hypertension. 2 Smoking of cigarettes induced an increase in blood pressure of the same degree in all experimental sessions. Heart rate increased by 16 beats/min during smoking alone, but increased significantly less, when a beta-adrenoceptor blocker was used. Forearm blood flow decreased during smoking in both medication periods. 3 Plasma adrenaline rose significantly during smoking from 0.37 nmol/l to 0.77 nmol/l; plasma noradrenaline did not change. 4 It is concluded that the blood pressure changes induced by smoking are not essentially altered during chronic treatment with selective or non-selective beta-adrenoceptor blockade. Only the increase in heart rate is significantly less pronounced during treatment with both drugs.

The effects of atenolol and propranolol upon lipolysis.

1 The effects of selective and non-selective beta-adrenoceptor blockade upon plasma non-esterified fatty acid concentrations in the fasting state and following insulin stress have been studied in normal subjects. 2 Atenolol, propranolol and placebo were compared in a double-blind cross-over trial in eight normal subjects. 3 Atenolol and propranolol significantly lowered plasma non-esterified fatty acid concentrations by a similar degree in the fasting, non-stressed state. This finding suggests that beta1-adrenoceptors are involved in the control of basal lipolysis. 4 Following insulin-induced stress, lower plasma non-esterified fatty acid concentrations were observed with propranolol than with atenolol. This difference may be due to beta2-adrenoceptor involvement in the stress mechanisms controlling lipolysis, or to the differences in the water-lipid solubility properties of these drugs.